This application relates to thin film membrane enzyme reactors.
More particularly, this application relates to thin film membranes, preferably ultraporous, formed of cross linked polymer systems, and to methods and techniques for the utilization of such membranes for confining active enzymes as enzyme reactor structures, and the manufacture and use thereof.
In addition, this application relates to composite ultraporous thin film membranes, having an ultraporous thin film membrane diffusion barrier confining an active enzyme formulation supported on a support, and to methods and techniques for the manufacture thereof.
Most common, industrial, enzymatic reactions are carried out in bulk reaction systems, ordinarily in batch reactions. The enzyme component which catalyzes the desired reaction is usually discarded as waste at the conclusion of the reaction. This occurs even though the enzyme functions as a catalyst and theoretically it is therefore possible to recover and recycle the enzyme at the conclusion of the reaction. However, in actual industrial scale reactions the theoretically possible recovery and recycling steps are rarely, if ever, carried out. Apart from the expense of recovery, it has often been found that the activity of recovered and recycled enzymes is degraded by the recovery procedures and in many cases undesirable or intolerable contaminants are introduced. Thus for many industrial enzymatic procedures, batch operations in bulk remain the norm.
For many enzyme catalyzed processes, the desirability and need for continuous, as opposed to batch, processing and other features has led to extensive investigations of techniques and means for the immobilization of enzymes on supports of one kind or another. The most commonly employed procedure at present is glutaraldehyde immobilization by the formation of covalent bonds to the enzyme, which form the basis for cross-linking the product to a physical support. The support is most often a granular solid, although there have been numerous investigations and use of other forms of supports, including membrane supports, particularly to physically entrap enzymes within the pores of membrane structures, most often with the additional use of chemical immobilization. It has been observed, however, that in many systems enzyme activity is impaired or even completely lost as a consequence of interference of the covalent cross-linking with the reactive site of the enzyme. There have been observations which reveal that the temperature and pH optima are also altered by such procedures. In some circumstances, advantage may be taken of the changes in properties, but on the whole, it is desirable to provide a technique which retains the original properties of the enzyme to the greatest possible degree.
In other contexts, there have been investigations of systems for physical entrapment or encapsulation of enzymes. The objectives of these procedures have generally been to avoid the unfavorable consequences of covalent bonding immobilization procedures, while retaining the advantages thereof. These systems and approaches have met with limited success and acceptance for a variety of reasons. Among these are characteristics which result in the loss of direct and intimate contact between the enzyme and the substrate, because of the limited diffusion capacities of such materials and structures, with the attendant losses in production rate and efficiency, and the rather substantial cost penalties involved.
One approach to physical entrapment of enzymes has been to confine the material on or in a membrane structure, where the enzyme remains lodged while the substrate is flowed through the membrane. The resulting stream is processed to recover the product, and the substrate is recycled. By these techniques the art has attempted to provide direct and intimate contact between the enzyme and the substrate, and by using commercially available membranes, the cost of this type of immobilization are kept to a reasonable level. These techniques have not met with acceptance, however, since the efficiencies of the system may be impaired in other ways. Notably, there is a trade-off between the permeability of the membrane, i.e., the resistance to flow of the substrate process stream, and the effectiveness of the containment of the enzyme. When the controlling or limiting pore size of the membrane is optimal for confining the enzyme, the hydraulic resistance to flow of the substrate containing stream is often unacceptably high. When the pore size is enlarged to a level more consistent with the flow rates required for reasonable through-put, there is an increasing risk of enzyme loss into the product stream. In some circumstances, the result is an inconvenient burden on the product purification, but in other circumstances, such results are intolerable.